Recent years have witnessed a dramatic increase in the use of technologies that allow the detailed interrogation of individual biological macromolecules in aqueous environments under near-native conditions. This increase can be attributed to the development and availability of highly sensitive experimental tools, such as atomic force microscopy (AFM), laser and magnetic tweezers, and fluorescence-based optical detection, all of which have all been used to study biological phenomena such as protein folding and unfolding, DNA dynamics, and protein-nucleic acid interaction.